With the establishment of the concept that anterior pituitary hormone secretion is significantly controlled by hypothalamic neurohormones, it is practically requisite to attempt to specifically regulate the secretory activity of this gland for the purpose of controlling tumorigenesis. The availability of certain ergot alkaloids which appear to specifically mimic the activity of the hypophysiotropic hormone PIF (prolactin inhibitory factor), the predominant hypothalamic regulation of pituitary prolactin secretion, provides an exceptional opportunity to evaluate this principle. It is well established that prolactin is the principal pituitary hormone in murine mammary tumorigenesis, as increased or decreased secretion of the hormone markedly enhances or suppresses, respectively, the development and growth of mammary carcinoma. The objectives of the research plan, therefore, are to evaluate the prophylactic and chemotherapeutic potential of certain ergot alkaloids in the control of murine mammary carcinoma. In the prophylactic phase of the investigation, we intend to evaluate the effectiveness of certain ergot alkaloids in suppression of mammary tumorigenesis in C3H/HeJ female mice. By selectively controlling (suppressing) pituitary prolactin secretion, chronically or periodically, throughout the lifetime of mammary tumor-susceptible animals, mammary carcinoma incidence could be sharply reduced or totally eliminated. In the chemotherapeutic phase of the investigation, we intend to evaluate the effectiveness of certain ergot alkaloids as oncolytic agents for use in rats bearing carcinogen-induced mammary carcinoma. Particular attention will be directed toward comparing the oncolytic activity of the alkaloids with that of hypophysectomy ovariectomy and androgen and estrogen therapy.